The relationship between obesity and endogenous estrogen levels was evaluated in 79 healthy, postmenopausal women. Thirty-nine of the women were siblings of patients with postmenopausal-onset breast cancer; the remaining women were age-matched (plus or minus 10 years) controls. Our hypothesis was that the siblings of the breast cancer patients would weigh more and that this excess weight would lead to higher serum estrone and estradiol levels. This hypothesis might explain the increased risk of breast cancer among first degree relatives. Association with obesity, especially among postmenopausal women and reported increased risk of breast cancer following hormone therapy among sisters of breast cancer patients. The choice of unaffected family members of breast cancer patients reduces the concern that results may have been influenced by the cancer rather than antecedent to its development. Our findings demonstrated a statistically significant excess estrone level in the siblings compared to the controls (58.9 vs. 47.8 pg/ml, p=.002). Serum estradiol levels were also significantly higher in the siblings (7.9 vs. 5.4 pg/ml, p=.04). The siblings weighed 4.3 kgs more than the controls. Matched pairs analysis (sibling-control), adjusting for weight, also showed significant differences in serum estrone levels. These differences were observed despite comparability in dietary intake, medication use and personal medical history. These findings represent the first time that higher estrogen levels have been measured in siblings of breast cancer patients. This observation may represent an important link in our understanding of the relationship between genetic and environmental risk factors of breast cancer. The current application represents an expansion of this initial research by adding variables to better define the determinants of endogenous sex hormone levels in a larger sample of women. Based on our initial observations and recent reports in the literature, we believe that it is very likely that hypoestrogenic siblings of breast cancer patients represent high risk individuals who may be detectable and available to dietary or pharmacological intervention to prevent breast cancer.